Bromodomain-containing protein 9 (BRD9) is a newly identified subunit of the non-canonical barrier-to-autointegration factor (ncBAF) complex and a member of the bromodomain family IV. Studies have confirmed that BRD9 plays an oncogenic role in multiple cancer types, by regulating tumor cell growth. The tumor biological functions of BRD9 are mainly due to epigenetic modification mediated by its bromodomain. The bromodomain recruits the ncBAF complex to the promoter to regulate gene transcription. This review summarizes the potential mechanisms of action of BRD9 in carcinogenesis and the emerging strategies for targeting BRD9 for cancer therapeutics. Although the therapeutic potential of BRD9 has been exploited to some extent, research on the detailed biological mechanisms of BRD9 is still in its infancy. Therefore, targeting BRD9 to study its biological roles will be an attractive tool for cancer diagnosis and treatment, but it remains a great challenge.

MicroRNAs (miRNAs) are small noncoding RNAs that commonly have 18-22 nucleotides and play important roles in the regulation of gene expression via directly binding to the 3'-UTR of target mRNAs. Approximately 50% of human genes are regulated by miRNAs and they are involved in many human diseases, including various types of cancers. Recently, microRNA-383 (miR-383) has been identified as being aberrantly expressed in multiple cancers, such as malignant melanoma, colorectal cancer, hepatocellular cancer, and glioma. Increasing evidence suggests that miR-383 participates in tumorigenic events including proliferation, apoptosis, invasion, and metastasis as well as drug resistance. Although downstream targets including CCND1, LDHA, VEGF, and IGF are illustrated to be regulated by miR-383, its roles in carcinogenesis are still ambiguous and the underlying mechanisms are still unclear. Herein, we review the latest studies on miR-383 and summarize its functions in human cancers and other diseases. The goal of this review is to provide new strategies for targeted therapy and further investigations.

As an inflammatory factor, IL‐25 has been studied in variouscancers, but it is rarely reported in cancer chemotherapy resistance. Major vault protein (MVP), as a gene associated with lung multidrug resistance, is associated with multiple chemotherapy resistances of lung cancer. However, the relationship between IL‐25 and MVP in lung cancer cells has not been studied. In this study, we found that both IL‐25 and MVP were elevated expressed in cisplatin‐resistant lung adenocarcinoma cell line (A549/CDDP). Silencing of IL‐25 resulted in down‐regulation of MVP expression and reduced cisplatin tolerance of A549/CDDP cells. Overexpression of IL‐25 resulted in increase of MVP expression and the cisplatin tolerance in A549 cells. In addition, we found that the extracellular IL‐25 could stimulate the expression of MVP and activate the NF‐κB signaling pathway. Further, animal models also confirmed that IL‐25 reduced the sensitivity of xenografts to chemotherapy. Taken together, we believe that the up‐regulation of IL‐25 induces MVP expression contributing to chemotherapy resistances of lung cancer cells. Our findings suggest that interference the expression of IL‐25 might be potential treatment strategies for the clinical reversing the chemotherapy resistance.

The expression of microRNA‑383 (miR‑383) is downregulated in a variety of tumor tissues, and it exhibits antiproliferative activity in non‑small cell lung cancer cells. In the present study, an association between the downregulation of miR‑383 expression and the deletion of chr8p22 in patients with lung adenocarcinoma was identified. The promoting effect of miR‑383 on cisplatin sensitivity was verified both in vivo and in vitro. Additionally, it was revealed that the expression of RNA binding motif protein 24 (RBM24) protein was regulated by and negatively correlated with miR‑383 expression. Ectopic expression of RBM24 or inhibition of miR‑383 decreased the chemosensitivity of parental A549 cells, whereas knockdown of RBM24 in cisplatin‑resistant A549 cells increased chemosensitivity. Mechanistically, miR‑383 interfered with the activation of nuclear factor κB (NF‑κB) signaling through repression of RBM24‑mediated phosphorylation of Rel‑like domain‑containing protein A and inhibitor α of NF‑κB. Taken together, the downregulation of miR‑383 induced RBM24 expression, which was mediated through the activation of NF‑κB signaling, to contribute to chemotherapy resistance in lung adenocarcinoma cells. The results of the present study highlight potential therapeutic targets for the clinical reversal of the chemotherapy resistance in lung adenocarcinoma.

Lung cancer is emerging as a common malignancy worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Two-dimensional (2D) in vitro cell line cultures and animal models are currently used to study NSCLC. However, 2D cell cultures fail to replicate the medication response and neoplastic heterogeneity of parental tumors. Animal models are expensive and require lengthy modeling cycles. The generation of in vitro three-dimensional (3D) tissue cultures called organoids, which exhibit multicellular, anatomical, and functional properties of real organs, is now achievable owing to advancements in stem cell culturing. The genetic, proteomic, morphological, and pharmacological characteristics of tumors are largely preserved in tumor organoids grown in vitro. The design and physiology of human organs can be precisely reconstructed in tumor organoids, opening new possibilities for complementing the use of animal models and studying human diseases. This review summarizes the development of NSCLC organoids and their applications in basic research, drug testing, immunotherapy, and individualized treatments.